tbuckley/cabot-search huggingface dataset:
Urology residents simulation training improves clinical outcomes in laparoscopic partial nephrectomy
Authors: A.d.O. Paludo, P. Knijnik, P. Brum, E. Cachoeira, A. Gorgen, L. Burttet, R. Cabral, S. Puliatti, T. Rosito, M. Berger, B. Silva Neto
Journal: European Urology (2022)
CNS border-associated macrophages in the homeostatic and ischaemic brain
Authors: Gabriela Gerganova, Alexandra Riddell, Alyson A. Miller
Journal: Pharmacology & Therapeutics (2022)

CNS border-associated macrophages (BAMs) are a small population of specialised macrophages localised in the choroid plexus, meningeal and perivascular spaces. Until recently, the function of this elusive cell type was poorly understood and largely overlooked, especially in comparison to microglia, the primary brain resident immune cell. However, the recent single cell immunophenotyping or transcriptomic analysis of BAM subsets in the homeostatic brain, coupled with the rapid emergence of new studies exploring BAM functions in various cerebral pathologies, including Alzheimer's disease, hypertension-induced neurovascular and cognitive dysfunction, and ischaemic stroke, has unveiled previously unrecognised heterogeneity and spatial-temporal complexity in BAM populations as well as their contributions to brain homeostasis and disease. In this review, we discuss the implications of this new-found knowledge on our current understanding of BAM function in ischaemic stroke. We first provide a comprehensive overview and discussion of the cell-surface expression profiles, transcriptional signatures and potential functional phenotypes of homeostatic BAM subsets described in recent studies. Evidence for their putative physiological roles is examined, including their involvement in immunological surveillance, waste clearance, and vascular permeability. We discuss the evidence supporting the accumulation and genetic transformation of BAMs in response to ischaemia and appraise the experimental evidence that BAM function might be deleterious in the acute phase of stroke, while considering the mechanisms by which BAMs may influence stroke outcomes in the longer term. Finally, we review the therapeutic potential of immunomodulatory strategies as an approach to stroke management, highlighting current challenges in the field and key issues relating to BAMs, and how BAMs could be harnessed experimentally to support future translational research.
Adjuvant immunotherapy in patients with resected esophageal and gastroesophageal junction cancer: Real-world evidence from Nova Scotia.
Authors: Margaret Sheridan, Stephanie Leann Snow
Journal: Journal of Clinical Oncology (2022)

e16047 Background: Post-operative immunotherapy (POI) with nivolumab has become the standard of care for eligible patients with esophageal and gastroesophageal junction cancers (EGEJC) who had pre-operative chemoradiation (POCRT) and definitive surgery. However, not all patients who receive POCRT are eligible for POI. Objective: The primary objective was to determine the proportion of patients who receive POCRT that are eligible for POI in a real-world population. Further, we aimed to identify the specific barriers to POI to determine factors which could be strategically addressed to maximize access to curative intent treatment. Methods: All patients residing in mainland Nova Scotia who received POCRT between July 2016 and April 2019 were analyzed. Disease, patient, and treatment characteristics were collected via chart review. The relative proportion of patients who (1) had definitive surgery, (2) were eligible to receive POI and (3) would have accepted POI were collected. The specific reasons for non-eligibility or refusal of POI were captured. Results: A total of 65 patients received POCRT during the study period. 44 of those went on to have definitive surgery. All 44 of these patients were then screened for eligibility to be enrolled in a trial of POI. 23 were eligible, but 12 declined trial enrolment. 21 were ineligible, with the most common reason being a pathological complete response (n=11). Of the 21 patients who did not undergo surgery, 12 were found to have new metastatic disease on pre-operative restaging and 9 were felt to be too frail. Conclusions: Only 35% of patient receiving POCRT were eligible for POI. This is important real-world data when planning allocation of resources and adapting health care budgets for novel treatments and indications.
Bariatric and metabolic surgery in Colombia during COVID–19, is it a risk? – Correspondence
Authors: Gonzalo Andrés Domínguez Alvarado, Kamila Serrano Mesa, María Paula Toloza Calvache, Luis Ernesto López Gómez, Sergio Serrano Gomez, Nelson Enrique Arroyo Chávez
Journal: International Journal of Surgery (2022)
The immune cell atlas of human neuroblastoma
Authors: Bronte Manouk Verhoeven, Shenglin Mei, Thale Kristin Olsen, Karin Gustafsson, Anders Valind, Axel Lindström, David Gisselsson, Shahrzad Shirazi Fard, Catharina Hagerling, Peter V. Kharchenko, Per Kogner, John Inge Johnsen, Ninib Baryawno
Journal: Cell Reports Medicine (2022)

Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for the development of immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 human NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison with normal fetal adrenal gland data. We provide a comprehensive immune cell landscape and characterize cell-state changes from normal tissue to NB. Our analysis reveals 27 immune cell subtypes, including distinct subpopulations of myeloid, NK, B, and T cells. Several different cell types demonstrate a survival benefit. In contrast to adult cancers and previous NB studies, we show an increase in inflammatory monocyte cell state when contrasting normal and tumor tissue, while no differences in cytotoxicity and exhaustion score for T cells, nor in Treg activity, are observed. Our receptor-ligand interaction analysis reveals a highly complex interactive network of the NB microenvironment from which we highlight several interactions that we suggest for future therapeutic studies.
LINC-19. Epidemiological Profile And Management Trends in Pediatric Brain Tumour Patients – 15 Year Experience From a Tertiary Neuro-Oncology Centre In South Asia
Authors: Vikas Singh, Rajesh Pathiyal, Prakash Shetty, Epari Sridhar, Girish Chinnaswamy, Tejpal Gupta, Aliasgar Moiyadi
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Brain tumour in pediatric age group are the most common solid tumour. Commonly occurring tumours include astrocytomas, medulloblastoma and ependymoma. Astrocytoma and medulloblastoma are common in Europe as compared to the Asian countries. AIM: To study the epidemiological profile and trends in management of pediatric brain tumor patients treated at a tertiary Neuro-oncology center. MATERIALS AND METHODS: This a retrospective audit of a prospectively maintained neurosurgical database from January 2007 to December 2021. All pediatric cases (&amp;lt; 18 years) operated by the neurosurgical oncology unit during the study period were included for analysis. CSF diversions and non oncologic surgical procedures were excluded. Demography, referral pattern, surgical and pathological variables of these patients was analyzed from the database and electronic medical records. Patients with missing data were excluded from analysis. RESULTS: 668 patients underwent oncologic surgical procedures. There was a male preponderance (60%) and 35% of children were in the age group of 5-11 years. Hospital received maximum referral from the parent city and state (46%) followed by north india (21%). Supratentorial tumours (52 %) were seen more commonly as compared to infratentorial tumours (39 %). Astrocytoma (31 %) and embryonal tumours( 25 %) were the common histological types. On subset analysis, both astrocytic (70%) and embryonal tumours (57%) were more common in children more than five years. Intraoperative neuromonitoring, intraoperative ultrasound and navigation were used during the surgical procedures as necessary. CONCLUSION: This study is one of the largest single institution analysis of pediatric brain tumours demonstrating trends in the demographic, surgical and pathological variables over 15 years and the observed pattern is similar to published literature from Indian subcontinent.
Quantification of methylation-specific cardiomyocyte cell-free DNA as an early marker of cardiotoxicity in patients with breast cancer receiving anthracyclines and trastuzumab.
Authors: Zachary Ray Moore, Anthony Francis Yu, Jennifer Liu, Chau T. Dang, Kevin C. Oeffinger, Richard Steingart, Adam Schmitt
Journal: Journal of Clinical Oncology (2022)

12090 Background: There is currently no way to reliably predict which patients undergoing therapy for breast cancer will develop cardiotoxicity. An early biomarker of cardiotoxicity could provide opportunity for intervention prior to the appearance of gross abnormalities on echocardiogram (ECHO). A droplet digital PCR (ddPCR) assay for circulating cell-free DNA (cfDNA) can detect cfDNA released from dying cardiomyocytes with high sensitivity by differentiating cfDNA of cardiomyocyte origin based on the pattern of methylation specific to the cell type. Circulating cfDNA of cardiac origin was tested as an early biomarker of toxicity in patients who underwent breast cancer treatment while closely monitoring cardiac function in a prospective clinical trial. Methods: A cardiomyocyte methylation-specific quantitative ddPCR assay was tested in plasma samples from 29 patients who were part of a larger prospectively enrolled cohort of women who received anthracyclines and trastuzumab for HER2-positive breast cancer. Blood samples were tested from prior to doxorubicin and cyclophosphamide (AC) chemotherapy, two months later after completing AC and prior to trastuzumab, and every 3 months to 12 months post-treatment. Patients were assessed for clinical cardiotoxicity, defined as heart failure (NYHA class III/IV) or significant EF decline (&gt; = 10% to below 53% or &gt; = 16%) until completion of cancer therapy. The maximum detected level of cardiac cfDNA (copies per 500 µL plasma) was compared between those who experienced cardiotoxicity and those who did not by two-sided T-tests. Results are reported as mean +/- standard deviation. Results: At baseline, cardiac cfDNA levels were low (mean 1.1 +/- 2.4 copies). Of 29 patients, five developed clinical cardiotoxicity. The maximum number of cfDNA copies at any time point was elevated in patients who experienced cardiotoxicity compared to those who did not (mean of 20.6 +/- 7.3 copies versus 9.3 +/- 9.8 copies, p = 0.0216). Of the patients with cardiotoxicity, elevated cfDNA of greater than 10 copies was detected an average of 3.6 +/- 2.5 months prior to the onset of clinical cardiotoxicity. Conclusions: Methylation specific cardiac cfDNA shows promise as an early indicator of cardiotoxicity in patients treated with anthracyclines in this pilot study. A previously reported analysis in the levels of seven other biomarkers including high-sensitivity troponin I and NT-proBNP pre- versus post-treatment in the full cohort of 80 patients did not show any statistically significant associations with the development of cardiotoxicity, suggesting that cardiac cfDNA may be uniquely informative. Clinical trial information: NCT02177175.
Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: Efficacy, safety and biomarker analysis.
Authors: Hao Tian, Guozhi Zhang, Yan Liang, Jing Liu, Linjun Fan, Kai Zhu, Yi Zhang, Xiaowei Qi
Journal: Journal of Clinical Oncology (2022)

e12605 Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was the total pCR (tpCR; ypT0/is ypN0). A Simon’s two-stage optimum design was used, and ＞5 of 11 pts were required to achieve tpCR in the first stage, with a pre-specified tpCR rate of 54.5% before proceeding to the second stage. A total of 31 participants was required for the study. Results: Six out of 11 pts achieved tpCR in the first stage, reaching the threshold for the second stage. From Jan 2021 to Jan 2022, a total of 22 pts were enrolled and 12 received surgery after the completion of neoadjuvant therapy, but a total of 2 pts withdrew from the study due to the COVID-19 pandemic or serious adverse events. Of the 22 eligible pts, the median age was 49 years (range, 29-64), 64% were postmenopausal, and 73% were nodal involved. At the time of surgery, 58.3% (7/12) achieved tpCR. Of the 9 pts with the node-positive disease at diagnosis, 88.9% (8/9) became ypN0. The results of FUSCC TNBC classification (IHC-based) revealed the tpCR rates were 57.1% (4/7), 100% (3/3), and 0% (0/2) for BLIS subtype, IM subtype and LAR/unknown subtypes, respectively. Biomarker analysis showed the tpCR rates were 100% (3/3) and 100% (4/4) in patients with gBRCA1 mutation and MYC amplification, respectively. The most common grade 3 or 4 treatment-related adverse events were leucopenia (6/22, 27%), neutropenia (6/22, 27%), anemia (5/22, 23%), decreased appetite (5/22, 23%), hypertension (2/22, 9%), ALT increased (1/22, 5%) and oral mucositis (1/22, 5%). No treatment-related deaths occurred. The trial is ongoing. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with early-stage TNBC. Clinical trial information: ChiCTR2100043027.
First-in-human, phase I study of AK109, an anti-VEGFR2 antibody, in patients (pts) with advanced or metastatic solid tumors.
Authors: Nong Xu, Yulong Zheng, Haijun Zhong, Fuyou Zhao, Huan Zhou, Chenyu Mao, Wangxia Lv, Meiqin Yuan, Jiong Qian, Haiping Jiang, Zishu Wang, Cheng Xiao, Ting Liu, Wei Liu, Baiyong Li, Yu Xia
Journal: Journal of Clinical Oncology (2022)

3021 Background: AK109 is a fully-human monoclonal antibody that specifically binds to vascular endothelial growth factor receptor 2 (VEGFR2), thereby block vascular endothelial growth factor (VEGF)/VEGFR2 signaling pathway to inhibit angiogenesis, endothelial cell migration and proliferation of tumor cells. This phase I study is the first-in-human trial of AK109, which was designed to evaluate safety, tolerability of AK109, to determine the maximum tolerated dose (MTD), recommend phase II dose (RP2D) and to gain preliminary data on pharmacokinetics (PK), pharmacodynamics, immunogenicity and clinical activity for AK109 in pts with advanced or metastatic solid tumors resistant to standard therapies (NCT04547205). Methods: This open-label, multi-center, phase I study included a dose escalation phase (part 1) using a 3+3 design to determine MTD and potential RP2D (n = 36 max), with planned dosing of 2, 4, 8, 12 and 18 mg/kg q2w and 15mg q3w, followed by a dose expansion phase (part 2), at 2 potential RP2Ds in q2w or q3w respectively (n = 24-30). The PK characteristics, dose limiting toxicity (DLT), adverse events per CTCAE 5.0 and efficacy (ORR, DCR, DoR, PFS per RECIST v1.1, OS, etc.) of AK109 were evaluated. Results: As of December 30 th , 2021 (median follow-up: 6.0 months), 40 pts (median age: 59.5 years) were enrolled, 16 pts in part 1 and 24 pts in part 2. No DLT was observed AK109 in part 1. Tumor types included gastric cancer (n = 9), non-small cell lung cancer (n = 8), hepatocellular carcinoma (n = 8), colorectal cancer (n = 5), pancreatic carcinoma (n = 2) and oesophagus cancer (n = 2), etc. Preliminary PK analyses showed systemic exposure in C max and AUC last increased dose proportionally at doses of 8 mg/kg and above, with a mean half-life of 8.5 to 10 days. 12mg/kg q2w and 15mg/kg q3w were selected as RP2Ds. Average exposure of AK109 was 6.9 cycles. Eight pts received over 10 cycles of AK109. Treatment related adverse events(TRAE) occurred in 38 (95%) of all pts. Grade 3 and 4 TRAE occurred in 16 (40%) of all pts. The most common TRAEs were proteinuria (22/40, 55%), hypertension (13/40, 32.5%) and AST increased (11/40, 27.5%). Serious adverse event (SAE) occurred in 11 (27.5%) pts, 2 (5%) of which were AK109 related. ORR and DCR were 10.0% and 62.5%, respectively. The median PFS of non-small cell lung cancer (n = 8) and gastric cancer (n = 9) were 5.6 months (95% CI, 1.3, NE) and 5.5 months (95% CI, 1.4, NE), respectively. Conclusions: AK109 showed manageable safety and promising anti-tumor activity. Two phase II studies of AK109 combined with AK104 (anti PD-1/CTLA-4 bi-specific antibody) are ongoing to evaluate the efficacy of AK109 combined with AK104 in patients with multiple solid tumors (NCT05142423, NCT04982276). Clinical trial information: NCT04547205.
Does ulceration affect survival in acral melanoma?
Journal: British Journal of Dermatology (2022)

Melanoma is the most aggressive type of skin cancer and the leading cause of death from skin cancer.Acral melanoma (AM) is a subtype of cutaneous melanoma, affecting non-hairy acral skin such as the soles of the feet, palms of the hands and nail beds.AM is the most common melanoma subtype in Asia and Africa but other types of melanoma are much more common in white patients.AM has a worse survival outcome compared with melanoma from other skin sites.A variety of methods are used to try and work out a patient's prognosis, that is to help predict the severity and outcome of their skin melanoma.Ulceration (the breakdown of the skin covering a tumour) is known to be a negative prognostic factor in melanoma.It is used together with tumour thickness to decide on the likely best treatment and outcome and they are part of the America Joint Committee on Cancer (AJCC) melanoma staging system (this staging system gives clinicians a common language to describe and discuss cancer).However, the exact prognostic impact of ulceration in AM is still controversial.This study set out to find out more about this subject.Over 1000 patients from China were included in the study and about 60% of these patients had ulceration.It was found that ulceration is a negative prognostic factor for patients with AM.In patients with thin melanoma (1 mm or less in thickness) the outcome was worse in the patients with ulceration compared with patients without ulceration.However, patients with or without ulceration with tumours that were more than 1 mm in thickness or who had tumours that was classed as clinical stage III have similar survival chances.In conclusion, these findings suggest that the AJCC staging system may not fit that well for AM, and can be simplified.
Predictors of success of the non-invasive treatment for uncomplicated steinstrasse post shockwave lithotripsy for renal stones
Authors: M. Elbaset, D-E. Taha, M. Anas, M. Badawy, M. Edwan, R.F. Elbaz, A. Elkarta, A.E. Abolazm, A.M. Lashin, Y. Osman, K.Z. Sheir
Journal: European Urology (2022)
Adults with first-time nephrotic syndrome had increased risk for thromboembolic events, higher near time of diagnosis
Authors: Siraj Mithoowani, Wendy Lim
Journal: Annals of Internal Medicine (2022)

Source Citation Vestergaard SV, Birn H, Darvalics B, et al. Risk of arterial thromboembolism, venous thromboembolism, and bleeding in patients with nephrotic syndrome: a population-based cohort study. Am J Med. 2022;135:615-25.e9. 34979093
Optimizing supportive care for patients with metastatic lung cancer in the era of precision oncology.
Authors: Kelly Hsu, Lecia V. Sequist, Vicki A. Jackson, Elyse R. Park, Dustin Rabideau, Joseph A. Greer, Jennifer Temel, Laura A Petrillo
Journal: Journal of Clinical Oncology (2022)

TPS12150 Background: Targeted therapy improves survival for patients with oncogene-driven non-small cell lung cancer (NSCLC). However, metastatic NSCLC remains incurable and patients often experience uncertainty about what to expect from their long and unpredictable illness trajectories. The aim of this trial is to pilot test a supportive care intervention that blends palliative care and survivorship for patients with metastatic oncogene-driven NSCLC. Methods: We will conduct a pilot randomized, controlled trial to evaluate the feasibility, acceptability and preliminary efficacy of a novel supportive care intervention for patients with metastatic oncogene-drive NSCLC. We will enroll 90 patients with a recent (within 6 months) diagnosis of metastatic NSCLC with a mutation in EGFR, ALK, ROS1 or RET genes who are receiving targeted therapy. We will enroll the first ten patients in an open pilot and we will refine the intervention and study procedures based on pilot findings. We will randomize the remaining 80 patients 1:1 to the intervention or a usual care control. Participants randomized to the intervention arm will have four monthly visits with a palliative care clinician who has been trained to address the supportive care needs of patients with long illness trajectories. Sessions will cover 1) rapport building and baseline symptom and psychosocial assessment; 2) coping support and healthy lifestyle promotion; 3) cultivation of prognostic understanding; and 4) exploration of goals and values. Patients in both arms will complete surveys including secondary outcome measures at baseline, 12, and 20 weeks post-enrollment. The primary outcome of the study is feasibility of the palliative care intervention, defined as at least 60% enrollment among eligible patients and 75% completion of all four sessions and three surveys. We will also assess acceptability using measures of satisfaction and comfort with the intervention. We will evaluate the preliminary effects of this intervention on the following outcomes to inform a future large-scale efficacy trial: 1) distress related to prognostic uncertainty and 2) prognostic awareness (using the Prognostic Awareness Questionnaire: 34-item validated measure with items about likelihood of cure and impact of prognostic awareness on decisions, behaviors and mood); 3) confidence in chronic disease management using the Self-Efficacy of Management of Chronic Disease scale; and 4) documentation of discussions about goals and values in the medical record. We will analyze change within and between groups at 12 and 20 weeks using linear mixed models, controlling for baseline values and relevant demographic and clinical factors. Study accrual to the open pilot phase began in February 2022. Current enrollment: n = 0. Clinical trial information: NCT04900935.
Head to head comparison between RENAL and PADUA nephrometry scores in predicting TRIFECTA achievement in off-clamp Robot-assisted partial nephrectomy
Authors: R.S. Flammia, U. Anceschi, A. Tufano, L. Antonelli, A. Brassetti, F. Proeitti, G. Tuderti, M. Gallucci, C. Leonardo, G. Simone
Journal: European Urology (2022)
Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia
Authors: David M. Liu, Thomas WT. Leung, Pierce KH. Chow, David CE. Ng, Rheun-Chuan Lee, Yun Hwan Kim, Yilei Mao, Yu-Fan Cheng, Gao-Jun Teng, Wan Yee Lau
Journal: International Journal of Surgery (2022)